A study of HLA class I and class II 4-digit allele level in Stevens-Johnson syndrome and toxic epidermal necrolysis
| Autor: | A F, Cristallo, J, Schroeder, A, Citterio, G, Santori, G M, Ferrioli, U, Rossi, G, Bertani, S, Cassano, P, Gottardi, N, Ceschini, F, Barocci, G, Ribizzi, V, Cutrupi, R, Cairoli, V, Rapisarda, E A, Pastorello, S, Barocci |
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| Přispěvatelé: | Cristallo, A, Schroeder, J, Citterio, A, Santori, G, Ferrioli, G, Rossi, U, Bertani, G, Cassano, S, Gottardi, P, Ceschini, N, Barocci, F, Ribizzi, G, Cutrupi, V, Cairoli, R, Rapisarda, V, Pastorello, E, Barocci, S |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Toxic Epidermal Necrolysis
Adult Male Genotyping Young Adult Gene Frequency Risk Factors SJS Haplotype Humans Alleles Epidermal Necrolysis Toxic Aged Allele Risk Factor Stevens Johnson Syndrome Histocompatibility Antigens Class I Histocompatibility Antigens Class II Middle Aged HLA MHC Paracetamol Haplotypes Italy Case-Control Studies Stevens-Johnson Syndrome Female Case-Control Studie Human |
| Popis: | Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are represented by rare but life-threatening cutaneous adverse reactions to different drugs. Previous studies have found that in a Han Chinese population from Taiwan and other Asian Countries, a strong genetic association between HLA-class I alleles (B*15:02, B*58:01) and SJS and TEN was induced by carbamazepine and allopurinol, respectively. To identify genetic markers that covered the MHC region, we carried out a case-control association enrolling 20 Caucasian patients with SJS/TEN. Our patient series included 10 cases related to paracetamol, 7 to allopurinol and 3 to different drugs (plaquenil, itraconazol, nabumetone). Healthy controls were represented by 115 Caucasian bone marrow or stem cell donors. The HLA-A*, B*, C*, DRB1*, DQB1*, DQA1* and DPB1* genotyping were determined. The frequencies of HLA-A*33:03 as well as C*03:02 and C*08:01 were significantly higher in SJS/TEN patient subgroup showing allopurinol drug-induced severe cutaneous adverse reactions (SCAR) as compared to controls (28.6% vs 0%, P=0.00002, Pc=0.0011; 28.6% vs 0%, P=0.00002, Pc=0.001; 28.6% vs 0%, P=0.00002, Pc=0.001, respectively). In the same subgroup the frequencies of B*58:01, DRB1*15:02 and DRB1*13:02 alleles, although considerably higher than in control group (42.8% vs 5.2%, P=0.003; 28.6% vs 1.7%, P=0.005; 28.6% vs 3.5%, P=0.037, respectively), appeared no more statistically different after P correction (Pc=0.248; Pc=0.29; Pc=1.00, respectively). In addition, in 10 of the 20 SJS/TEN patient subgroup with paracetamol-induced SCAR no statistically significant association with HLA alleles could be found. However, in the same SJS/TEN patient subgroup showing allopurinol drug-induced SCAR, haplotype analysis indicated that B*58:01, DRB1*13:02 and DRB1*15:02 alleles, that in a single allele analysis lost statistical significance after P correction, may still confer susceptibility, because the B*58:01-DRB1*13:02 and DRB1*15:02-DQB1*05:02 are positively associated with the disease (14.2% vs 0.43%, P= 0.00001, Pc=0.00028; 14.2% vs 0.43%, P=0.00001, Pc=0.00028, respectively). Our results show that in contrast to SCAR-related to paracetamol, where HLA alleles do not appear to be involved, HLA molecules behave as a strong risk factor for SCAR-related to allopurinol even when a limited number of patients are considered. |
| Databáze: | OpenAIRE |
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